NO312294B1 - 2-(arylfenyl)amino-imidazolinderivater, fremgangsmåte for fremstilling og anvendelse derav, og farmasöytisk preparatinneholdende disse - Google Patents
2-(arylfenyl)amino-imidazolinderivater, fremgangsmåte for fremstilling og anvendelse derav, og farmasöytisk preparatinneholdende disse Download PDFInfo
- Publication number
- NO312294B1 NO312294B1 NO19984044A NO984044A NO312294B1 NO 312294 B1 NO312294 B1 NO 312294B1 NO 19984044 A NO19984044 A NO 19984044A NO 984044 A NO984044 A NO 984044A NO 312294 B1 NO312294 B1 NO 312294B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- aminoimidazoline
- formula
- compound
- benzyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 65
- 238000002360 preparation method Methods 0.000 title claims description 45
- MSYFITFSZJKRQJ-UHFFFAOYSA-N 4,5-dihydroimidazol-1-amine Chemical class NN1CCN=C1 MSYFITFSZJKRQJ-UHFFFAOYSA-N 0.000 title claims description 10
- 230000008569 process Effects 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 249
- 239000013078 crystal Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical group 0.000 claims abstract description 19
- 108091006335 Prostaglandin I receptors Proteins 0.000 claims abstract description 9
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 6
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 135
- -1 (4) - morpholinyl Chemical group 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 19
- 208000002193 Pain Diseases 0.000 claims description 18
- 230000036407 pain Effects 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 239000000460 chlorine Chemical group 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 11
- 206010040070 Septic Shock Diseases 0.000 claims description 11
- 229910052801 chlorine Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 230000036303 septic shock Effects 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
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- 208000006673 asthma Diseases 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- GYYRMJMXXLJZAB-UHFFFAOYSA-N n-[4-[(4-propan-2-yloxyphenyl)methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1=CC(OC(C)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 GYYRMJMXXLJZAB-UHFFFAOYSA-N 0.000 claims description 4
- OQEBIHQSIWAWMH-UHFFFAOYSA-N n-[4-[[4-(oxan-4-ylmethoxy)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1COCCC1COC(C=C1)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 OQEBIHQSIWAWMH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- LNKKILTYFJGMJF-UHFFFAOYSA-N n-[4-[(4-butan-2-yloxyphenyl)methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1=CC(OC(C)CC)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 LNKKILTYFJGMJF-UHFFFAOYSA-N 0.000 claims description 3
- ZODCLJXQLFWUHZ-UHFFFAOYSA-N n-[4-[[4-(oxan-4-yloxy)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C=1C=C(OC2CCOCC2)C=CC=1CC(C=C1)=CC=C1NC1=NCCN1 ZODCLJXQLFWUHZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- JDLYEHJOMPVQFU-UHFFFAOYSA-N 2-[4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]phenoxy]propan-1-ol Chemical compound C1=CC(OC(CO)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 JDLYEHJOMPVQFU-UHFFFAOYSA-N 0.000 claims description 2
- JFODXFPIYJCKGA-UHFFFAOYSA-N 4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]-n-(2-methylpropyl)benzamide Chemical compound C1=CC(C(=O)NCC(C)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 JFODXFPIYJCKGA-UHFFFAOYSA-N 0.000 claims description 2
- GVNBSLRDMFBJJL-UHFFFAOYSA-N 4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]-n-(2-methylpropyl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCC(C)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 GVNBSLRDMFBJJL-UHFFFAOYSA-N 0.000 claims description 2
- MLJPVCGKYSYMJC-UHFFFAOYSA-N 4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]-n-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(C)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 MLJPVCGKYSYMJC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000532 dioxanyl group Chemical group 0.000 claims description 2
- YDNNLWHCIDLUFN-UHFFFAOYSA-N n-[4-[(4-cyclopentyloxyphenyl)methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C=1C=C(OC2CCCC2)C=CC=1CC(C=C1)=CC=C1NC1=NCCN1 YDNNLWHCIDLUFN-UHFFFAOYSA-N 0.000 claims description 2
- JLNFCMIBOXQHSH-UHFFFAOYSA-N n-[4-[[2-fluoro-4-(oxan-4-ylmethoxy)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C=1C=C(CC=2C=CC(NC=3NCCN=3)=CC=2)C(F)=CC=1OCC1CCOCC1 JLNFCMIBOXQHSH-UHFFFAOYSA-N 0.000 claims description 2
- GTIQUGCQXTZRCN-UHFFFAOYSA-N n-[4-[[4-(1,3-diethoxypropan-2-yloxy)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1=CC(OC(COCC)COCC)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 GTIQUGCQXTZRCN-UHFFFAOYSA-N 0.000 claims description 2
- MXPUNYONDDMSHO-UHFFFAOYSA-N n-[4-[[4-(butan-2-yloxymethyl)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1=CC(COC(C)CC)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 MXPUNYONDDMSHO-UHFFFAOYSA-N 0.000 claims description 2
- MXZKWFONRLSEAK-UHFFFAOYSA-N n-[4-[[4-(oxan-2-ylmethoxy)phenyl]methyl]phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound C1CCCOC1COC(C=C1)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 MXZKWFONRLSEAK-UHFFFAOYSA-N 0.000 claims description 2
- HYAQHWBZFXCUKL-UHFFFAOYSA-N n-benzyl-4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]benzamide Chemical compound C=1C=C(CC=2C=CC(NC=3NCCN=3)=CC=2)C=CC=1C(=O)NCC1=CC=CC=C1 HYAQHWBZFXCUKL-UHFFFAOYSA-N 0.000 claims description 2
- YGJRAVQHTWJWBA-UHFFFAOYSA-N n-butyl-4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCCC)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 YGJRAVQHTWJWBA-UHFFFAOYSA-N 0.000 claims description 2
- RBYQCNLYMCZGMK-UHFFFAOYSA-N n-tert-butyl-4-[[4-(4,5-dihydro-1h-imidazol-2-ylamino)phenyl]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1CC(C=C1)=CC=C1NC1=NCCN1 RBYQCNLYMCZGMK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 255
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 180
- 238000006243 chemical reaction Methods 0.000 description 121
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 89
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- 238000004458 analytical method Methods 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
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- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000003371 phospholipase C inhibitor Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 description 1
- 235000019252 potassium sulphite Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
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- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 1
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- JRIQCVWTPGVBBH-UHFFFAOYSA-N pyrrolidine-1-sulfonyl chloride Chemical compound ClS(=O)(=O)N1CCCC1 JRIQCVWTPGVBBH-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
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- 230000003595 spectral effect Effects 0.000 description 1
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- 238000013223 sprague-dawley female rat Methods 0.000 description 1
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- 230000000087 stabilizing effect Effects 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
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- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 239000011592 zinc chloride Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61P13/00—Drugs for disorders of the urinary system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Lenses (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US5780897P | 1997-09-04 | 1997-09-04 | |
US8991698P | 1998-06-19 | 1998-06-19 |
Publications (3)
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NO984044D0 NO984044D0 (no) | 1998-09-03 |
NO984044L NO984044L (no) | 1999-03-05 |
NO312294B1 true NO312294B1 (no) | 2002-04-22 |
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Application Number | Title | Priority Date | Filing Date |
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NO19984044A NO312294B1 (no) | 1997-09-04 | 1998-09-03 | 2-(arylfenyl)amino-imidazolinderivater, fremgangsmåte for fremstilling og anvendelse derav, og farmasöytisk preparatinneholdende disse |
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EP (1) | EP0902018B1 (zh) |
JP (1) | JP3040752B2 (zh) |
KR (1) | KR100309191B1 (zh) |
CN (1) | CN1110484C (zh) |
AT (1) | ATE402151T1 (zh) |
AU (1) | AU746480B2 (zh) |
CA (1) | CA2245755A1 (zh) |
CZ (1) | CZ278198A3 (zh) |
DE (1) | DE69839753D1 (zh) |
DK (1) | DK0902018T3 (zh) |
HK (1) | HK1019334A1 (zh) |
HU (1) | HUP9801950A3 (zh) |
IL (1) | IL125982A (zh) |
MA (1) | MA26541A1 (zh) |
NO (1) | NO312294B1 (zh) |
NZ (1) | NZ331480A (zh) |
PT (1) | PT902018E (zh) |
RU (1) | RU2211834C2 (zh) |
TW (1) | TW432046B (zh) |
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WO2001068591A1 (en) | 2000-03-16 | 2001-09-20 | F. Hoffmann-La Roche Ag | Carboxylic acid derivatives as ip antagonists |
CN1468227A (zh) * | 2000-08-08 | 2004-01-14 | ����-������ҩƷ��˾ | 非咪唑芳氧基烷基胺 |
JP4909487B2 (ja) * | 2000-08-30 | 2012-04-04 | 学校法人神奈川大学 | オキセタン変性化合物とそれから誘導される光硬化性化合物、それらの製造方法及びそれらを含有する硬化性組成物 |
PL362549A1 (en) * | 2000-11-14 | 2004-11-02 | F.Hoffmann-La Roche Ag | Substituted 2-phenylaminoimidazoline phenyl ketone derivatives as ip antagonists |
US20060171945A1 (en) * | 2003-02-14 | 2006-08-03 | Critchley Hilary Octavia D | Ip receptor antagonists for the treatment of pathological uterine conditions |
EP1622611A1 (en) * | 2003-05-01 | 2006-02-08 | F. Hoffmann-La Roche Ag | Imidazolin-2-ylaminophenyl amides as ip antagonists |
EP1656350A2 (en) * | 2003-07-09 | 2006-05-17 | F.Hoffmann-La Roche Ag | Thiophenylaminoimidazolines as prostaglandin i2 antagonists |
EP2513064B1 (en) | 2009-12-17 | 2018-07-04 | Katholieke Universiteit Leuven, K.U. Leuven R&D | Compounds, compositions and methods for controlling biofilms |
US9452980B2 (en) * | 2009-12-22 | 2016-09-27 | Hoffmann-La Roche Inc. | Substituted benzamides |
EP2600864B1 (en) * | 2010-08-04 | 2019-01-09 | University Of Virginia Patent Foundation | Compositions and methods for treating inflammatory diseases |
WO2014032755A2 (en) * | 2012-08-29 | 2014-03-06 | Merck Patent Gmbh | Ddr2 inhibitors for the treatment of osteoarthritis |
US9321745B2 (en) | 2013-03-12 | 2016-04-26 | Allergan, Inc. | Inhibition of neovascularization by inhibition of prostanoid IP receptors |
WO2014143591A1 (en) | 2013-03-12 | 2014-09-18 | Allergan, Inc. | Inhibition of neovascularization by simultaneous inhibition of prostanoid ip and ep4 receptors |
WO2016043260A1 (ja) * | 2014-09-19 | 2016-03-24 | 塩野義製薬株式会社 | 環状グアニジンまたはアミジン化合物 |
US9827225B2 (en) | 2016-01-25 | 2017-11-28 | Jenivision Inc. | Use of prostacyclin antagonists for treating ocular surface nociception |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
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NL7711390A (nl) | 1977-10-18 | 1979-04-20 | Philips Nv | Nieuwe 2-arylimino-hexahydopyrimidinen en - imi- dazolidinen, zouten en complexen daarvan, werk- wijze ter bereiding van de nieuwe verbindingen, alsmede fungicide preparaten op basis van de nieuwe verbindingen. |
NL7810350A (nl) | 1978-10-16 | 1980-04-18 | Duphar Int Res | Preparaat met groeiregulerende werking en gebruik van dit preparaat in land- en tuinbouw. |
CA1138451A (en) | 1979-04-03 | 1982-12-28 | Ikuo Ueda | 2-imidazoline derivatives, process for the preparation thereof and the pharmaceutical composition of the same |
US4287201A (en) * | 1980-03-03 | 1981-09-01 | Merck & Co., Inc. | Anovulatory method and chicken feed compositions |
US4889868A (en) | 1984-12-20 | 1989-12-26 | Rorer Pharmaceutical Corporation | Bis-imidazolinoamino derivatives as antiallergy compounds |
WO1993017681A1 (en) | 1992-03-02 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
GB9506188D0 (en) | 1995-03-27 | 1995-05-17 | Fujisawa Pharmaceutical Co | Amidine derivatives |
-
1998
- 1998-08-20 NZ NZ331480A patent/NZ331480A/en unknown
- 1998-08-26 EP EP98116091A patent/EP0902018B1/en not_active Expired - Lifetime
- 1998-08-26 DE DE69839753T patent/DE69839753D1/de not_active Expired - Fee Related
- 1998-08-26 DK DK98116091T patent/DK0902018T3/da active
- 1998-08-26 AT AT98116091T patent/ATE402151T1/de not_active IP Right Cessation
- 1998-08-26 PT PT98116091T patent/PT902018E/pt unknown
- 1998-08-27 CA CA002245755A patent/CA2245755A1/en not_active Abandoned
- 1998-08-28 IL IL12598298A patent/IL125982A/en not_active IP Right Cessation
- 1998-08-31 HU HU9801950A patent/HUP9801950A3/hu unknown
- 1998-09-01 CZ CZ982781A patent/CZ278198A3/cs unknown
- 1998-09-01 MA MA25239A patent/MA26541A1/fr unknown
- 1998-09-02 JP JP10248047A patent/JP3040752B2/ja not_active Expired - Fee Related
- 1998-09-03 NO NO19984044A patent/NO312294B1/no not_active IP Right Cessation
- 1998-09-03 RU RU98117245/04A patent/RU2211834C2/ru not_active IP Right Cessation
- 1998-09-03 AU AU83094/98A patent/AU746480B2/en not_active Ceased
- 1998-09-04 CN CN98118587A patent/CN1110484C/zh not_active Expired - Fee Related
- 1998-09-04 KR KR1019980036524A patent/KR100309191B1/ko not_active IP Right Cessation
- 1998-09-08 TW TW087114724A patent/TW432046B/zh active
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1999
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IL125982A (en) | 2002-09-12 |
HUP9801950A3 (en) | 2001-12-28 |
CN1110484C (zh) | 2003-06-04 |
EP0902018A2 (en) | 1999-03-17 |
HK1019334A1 (en) | 2000-02-03 |
NZ331480A (en) | 2000-02-28 |
EP0902018B1 (en) | 2008-07-23 |
CZ278198A3 (cs) | 1999-04-14 |
NO984044L (no) | 1999-03-05 |
MA26541A1 (fr) | 2004-12-20 |
AU746480B2 (en) | 2002-05-02 |
PT902018E (pt) | 2008-09-05 |
CA2245755A1 (en) | 1999-03-04 |
NO984044D0 (no) | 1998-09-03 |
EP0902018A3 (en) | 2001-05-02 |
KR19990029550A (ko) | 1999-04-26 |
HUP9801950A2 (hu) | 1999-03-29 |
RU2211834C2 (ru) | 2003-09-10 |
JPH11140057A (ja) | 1999-05-25 |
DE69839753D1 (de) | 2008-09-04 |
DK0902018T3 (da) | 2008-10-20 |
IL125982A0 (en) | 1999-04-11 |
HU9801950D0 (en) | 1998-10-28 |
ATE402151T1 (de) | 2008-08-15 |
TW432046B (en) | 2001-05-01 |
JP3040752B2 (ja) | 2000-05-15 |
CN1216762A (zh) | 1999-05-19 |
AU8309498A (en) | 1999-03-18 |
KR100309191B1 (ko) | 2001-12-12 |
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